颈神经卡压对远端神经干损伤敏感性的影响及其机制研究

颈神经根病常伴同侧上肢神经、肌骨骼疾患发病率升高，单纯治疗后者疗效并不可靠，目前尚不清楚该现象发生的原因。“轴浆流受损”理论认为神经干近端受压时会降低同一轴索对远端损伤的敏感性，但近端病变位于神经根时难以解释。.本研究拟从“局限性神经根卡压诱发广泛性神经干炎症，进而引起伤害敏感性升高”这一思路探讨上述临床机制。首先观察大鼠颈神经损伤后，正中神经和非卡压节段感觉神经元损伤及炎症反应，并检测神经元兴奋性改变，以明确颈神经卡压能否对非卡压轴索产生炎性致敏，进而在神经干内将根性损伤范围扩大。随后从“正中神经微循环改变导致血-神经屏障破坏”以及“投射至正中神经的交感神经节后系统损伤”这两条途径探讨正中神经广泛性损伤敏感性升高的机制。最后通过模型验证颈神经损害对正中神经轻微压迫的影响。.该研究有望以诊断一元论为原则，从机制层面提出“广义性双卡综合征”这一新概念，为该类疾患整体化诊疗理念提供理论依据。

Cervical radiculopathy is usually associated with a higher prevalence of ipsilateral peripheral or musculoskeletal disorders. The former includes the carpal or cubital tunnel syndrome, which is defined as double crush syndrome (DCS). The concomitant musculoskeletal disorders generally presented are sub-acromion impingement, lateral or medial epicondylitis. The underlying mechanisms of this phenomenon are still unclear. A hypothesis proposes that a proximal lesion may increase the susceptibility of the distal segment along the same axons to subsequent damage through “the disruption of axoplasmic flow.” In this manner, a subclinical distal neuro- or musculopathy may be converted into a clinically evident one. However, this explanation has been questioned on the bases of anatomical and pathophysiologic restrictions. The axons of a distal nerve trunk or musculoskeletal innervation usually originated from multiple spinal nerves (e.g., the median nerve from C6 to T1). A limited proximal lesion, if at the root or plexus level, usually does not comply with the basic tenet of the DCS at the segment of distal innervation. Significant doubts exist about the validity of the diagnosis of DCS, as well as the susceptibility of other musculoskeletal disorders.. The most frequent type of DCS is cervical radiculopathy concurrent with carpal tunnel syndrome. In this study, therefore, we will propose a rat model of ligation of cervical spinal nerves (C6+T1 or C8+T1) to examine the pathological changes of the axons of the median nerve distal to the compressive site, as well as the primary sensory neurons at dorsal root ganglions (DRG). We aim to identify whether the intact axons are sensitized by the local inflammation response produced by the axons with proximal lesions. The excitability of the sensory neurons of DRG, which may be affected by the cytokines, will be tested through the patch-clamp recording technique. To find out the mechanisms that the spinal nerve compression is impacting on the vulnerability of the nerve trunk to a distal lesion, we plan to investigate the changes of the microcirculation of the median nerve after spinal nerve ligation. The disruption of the blood-nerve barrier may activate the resident and blood-borne macrophages, which induces hypersensitivity by releasing a large number of cytokines. We will also examine the inflammatory responses and excitability of sympathetic postganglionic neurons projecting to the median nerve. The irritated sympathetic fibers may directly sensitize the sensory neurons at the intact segments of the spinal nerve, or enhance the inflammatory response at the median nerve to radiculopathy. The disruption of the blood-nerve barrier or postganglionic sympathetic neurons may transmit the lesions from the crushed axons to the intact one in the median nerve. Therefore, a limited proximal compression at the spinal nerve will be exaggerated to an extensive lesion at the distal nerve trunk, and the susceptibility to nerve or musculoskeletal disorders will be developed, regardless of no same axon compromised at dual sites. Finally, we will propose an experimental model of DCS with spinal nerve ligation and slight compression to the median nerve, which may verify the increased vulnerability of the median nerve to a mild distal lesion. . The results of this study may provide a novel conception of “generalized double crush syndrome,” which accounts for the vulnerability of the ipsilateral limb concurrent with cervical radiculopathy. We may propose a new diagnostic criterion and warrant the effectiveness of therapy to the cervical spine for this variety of the disease upon this conceptual framework.